PROJECT SUMMARY/ABSTRACT We propose a novel technical, regulatory, and cultural solution to support research on COVID- 19 and establish the open infrastructure required to respond to the next pandemic: ICEES+ COVID-19. The proposed work will build on the prior work that our team has been engaged with as part of the Biomedical Data Translator program (?Translator?), funded by the National Center for Advancing Translational Sciences (NCATS), to research and develop the Integrated Clinical and Environmental Exposures Service (ICEES). ICEES represents a unique, disease-agnostic framework and approach to support open sharing of and research on sensitive patient data that have been integrated at the patient and visit level with public exposures data. Importantly, ICEES has been validated in the context of our initial driving use case on asthma. We will extend this effort to instantiate an ICEES+ COVID-19 open infrastructure, focused on patients at UNC Health who have been tested (positive or negative) for COVID-19. The proposed work will leverage not only our prior Translator work, but also new work that our team has been engaged with as part of the NCATS Center for Data to Health (CD2H) National Covid Cohort Collaborative (N3C). Indeed, the North Carolina Translational and Clinical Sciences Institute (home to UNC?s CTSA) was selected by CD2H leadership to lead the technical implementation of significant portions of the N3C initiative. We will adopt the N3C COVID-19 consensus phenotype for the proposed work and extend the captured data fields to include relevant data fields that were intentionally excluded by the N3C collaborative in their effort to promote uniformity and participation, but are available via our local clinical data warehouse, such as temperature, oxygen saturation, isolation flags, and other potentially relevant clinical features (e.g., blood type). We also have partnered with investigators affiliated with the Environmental Polymorphisms Registry at the National Institute for Environmental Health Sciences and will be exposing data on their registry participants. Our overall aims are to develop and deploy ICEES+ COVID-19, apply ICEES+ COVID-19 to support research on COVID-19, and promote widespread use of ICEES+ COVID-19, largely through our engagement with the Translator program, CD2H N3C, and other large-scale collaboratives. A key aspect of the proposed work is that ICEES+COVID-19 will be open source, which will allow other institutions to rapidly adopt our approach and expose their data for open analysis of COVID-19 data by a much larger community. Collectively, the proposed work will catalyze efforts to respond to the COVID-19 pandemic and position society to be better prepared for the next one.